Synthesis and phototoxicity of isomeric 7,9-diglutathione pyrrole adducts: Formation of reactive oxygen species and induction of lipid peroxidation

Pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic in experimental animals. Because of their widespread distribution in the world, PA-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Upon metabolism, PAs generate reactive dehydro-PAs and other pyrrolic metabolites that lead to toxicity. Dehydro-PAs are known to react with glutathione (GSH) to form 7-GSH-(+/−)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (7-GS-DHP) in vivo and in vitro and 7,9-diGS-DHP in vitro. To date, the phototoxicity of GS-DHP adducts has not been well studied. In this study, we synthesized 7-GS-DHP, a tentatively assigned 9-GS-DHP, and two enantiomeric 7,9-diGS-DHP adducts by reaction of dehydromonocrotaline with GSH. The two 7,9-diGS-DHPs were separated by high performance liquid chromatography (HPLC) and their structures were characterized by 1H nuclear magnetic resonance (NMR) and 1H–1H correlation spectroscopy (COSY) NMR spectral analysis. Photoirradiation of 7-GS-DHP, 9-GS-DHP, and the two 7,9-diGS-DHPs as well as dehydromonocrotaline, dehydroheliotrine, and the 7-R enantiomer of DHP (DHR), by UVA light at 0 J/cm2, 14 J/cm2, and 35 J/cm2 in the presence of a lipid, methyl linoleate, all resulted in lipid peroxidation in a light dose-responsive manner. The levels of lipid peroxidation induced by the two isomeric 7,9-diGS-DHPs were significantly higher than that by 7-GS-DHP and 9-GS-DHP. When 7,9-diGS-DHP was irradiated in the presence of sodium azide (NaN3), the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a product induced by the irradiation of 7,9-diGS-DHP. When irradiated in the presence of superoxide dismutase (SOD), the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. These results indicate that lipid peroxidation is mediated by reactive oxygen species (ROS). These results suggest that 7,9-diGS-DHPs are phototoxic, generating lipid peroxidation mediated by ROS

Comparison of counterstreaming suprathermal electron signatures of ICMEs with and without magnetic cloud: are all ICMEs flux ropes?

Context. Magnetic clouds (MCs), as in large-scale interplanetary magnetic flux ropes, are usually still connected to the Sun at both ends near 1 AU. Many researchers believe that all nonMC interplanetary coronal mass ejections (ICMEs) also have magnetic flux rope structures, which are inconspicuous because the observing spacecraft crosses the flanks of the rope structures. If so, the field lines of nonMC ICMEs should also usually be connected to the Sun at both ends. Aims. We want to know whether or not the field lines of most nonMC ICMEs are still connected to the Sun at both ends. Methods. This study examined the counterstreaming suprathermal electron (CSE) signatures of 272 ICMEs observed by the Advanced Composition Explorer (ACE) spacecraft from 1998 to 2008 and compared the CSE signatures of MCs and nonMC ICMEs. Results. Results show that only 10 of the 101 MC events (9.9% ) and 75 of the 171 nonMC events (43.9%) have no CSEs. Moreover, 21 of the nonMC ICMEs have high CSE percentages (more than 70%) and show relatively stable magnetic field components with slight rotations, which are in line with the expectations that the observing spacecraft passes through the flank of magnetic flux ropes. Therefore, the 21 events may be magnetic flux ropes but the ACE spacecraft passes through their flanks of magnetic flux ropes. Conclusions. Considering that most other nonMC events have disordered magnetic fields, we suggest that some nonMC ICMEs inherently have disordered magnetic fields, and therefore no magnetic flux rope structures

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

Abstract Background Endometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. Patients with UCEC exhibit the similar clinical features, however, they have distinct outcomes due to molecular heterogeneity. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients’ survival and improving patient-tailored treatment. Methods We performed a comprehensive genome-wide analysis of lncRNA expression profiles and clinical data in a large cohort of 301 UCEC patients. UCEC patients were randomly divided into the discovery cohort (n = 150) and validation cohort (n = 151). A novel lncRNA-focus expression signature was identified in the discovery cohort, and independently accessed in the validation cohort. Additionally, the lncRNA signature was evaluated by multivariable Cox regression and stratification analysis as well as functional enrichment analysis. Results We detected a novel lncRNA-focus expression signature (LFES) consisting of 11 lncRNAs that were associated with survival based on risk scoring strategy in UCEC. The risk score based on the LFES was able to separate patients of discovery cohort into high-risk and low-risk groups with significantly different overall survival and progression-free survival, and has been successfully confirmed in the validation cohort. Furthermore, the LFES is an independent prognostic predictor of survival and demonstrates superior prognostic performance compared with the clinical covariates for predicting 5-year survival (AUC = 0.887). Functional analysis has linked the expression of prognostic lncRNAs to well-known tumor suppressor or ontogenetic pathways in endometrial carcinogenesis. Conclusions Our study revealed a novel 11-lncRNA signature to predict survival of UCEC patient. This lncRNA signature may be a valuable and alternative marker for risk evaluation to aid patient-tailored treatment and improve the outcome of patients with UCEC

The Relationship of Magnetic Twist and Plasma Motion in a Magnetic Cloud

Our recent investigations indicate that interplanetary magnetic clouds (MCs) have a high-twist core and a weak-twist outer shell. Utilizing the velocity-modified uniform-twist force-free flux rope model, we further investigate the relationship between the twist profile of magnetic field lines and the distribution of the plasma poloidal angular velocity inside an MC. The poloidal velocity in the MC is 11 km s−1. There are evidently positive correlations between the absolute value of the twist and the plasma poloidal angular velocity in peeled flux ropes or flux rope layers, although the correlation coefficients in flux rope layers are less than those in peeled flux ropes. This finding suggests that plasma flows are frozen-in magnetic field lines as we expected for interplanetary medium, of which the magnetic Reynolds number is large. Furthermore, based on this picture, we infer the axial velocity in the MC frame, which is less than 10 km s−1 and almost uniform in the cross section of the MC. Besides, it is inferred that the plasma flows velocity in the MC is much less than the local Alfvén speed

An Efficient Method for the Preparative Isolation and Purification of Flavonoids from Leaves of Crataegus pinnatifida by HSCCC and Pre-HPLC

In this work, flavonoid fraction from the leaves of Crataegus pinnatifida was separated into its seven main constituents using a combination of HSCCC coupled with pre-HPLC. In the first step, the total flavonoid extract was subjected to HSCCC with a two-solvent system of chloroform/methanol/water/n-butanol (4:3:2:1.5, v/v), yielding four pure compounds, namely (–)-epicatechin (1), quercetin-3-O-(2,6-di-α-l-rhamnopyranosyl)-β-d-galactopyranoside (2), 4′′-O-glucosylvitexin (3) and 2′′-O-rhamnosylvitexin (4) as well as a mixture of three further flavonoids. An extrusion mode was used to rapidly separate quercetin-3-O-(2,6-di-α-l-rhamnopyranosyl)-β-d-galactopyranoside with a big KD-value. In the second step, the mixture that resulted from HSCCC was separated by pre-HPLC, resulting in three pure compounds including: vitexin (5), hyperoside (6) and isoquercitrin (7). The purities of the isolated compounds were established to be over 98%, as determined by HPLC. The structures of these seven flavonoids were elucidated by ESI-MS and NMR spectroscopic analyses